WO2001000603A1 - Derives de thiazol et d'oxazole et utilisation pharmaceutique de ceux-ci - Google Patents

Derives de thiazol et d'oxazole et utilisation pharmaceutique de ceux-ci Download PDF

Info

Publication number
WO2001000603A1
WO2001000603A1 PCT/EP2000/005720 EP0005720W WO0100603A1 WO 2001000603 A1 WO2001000603 A1 WO 2001000603A1 EP 0005720 W EP0005720 W EP 0005720W WO 0100603 A1 WO0100603 A1 WO 0100603A1
Authority
WO
WIPO (PCT)
Prior art keywords
methyl
phenyl
trifluoromethyl
thiazol
sulfanyl
Prior art date
Application number
PCT/EP2000/005720
Other languages
English (en)
Inventor
Esther Yu-Hsuan Chao
Curt Dale Haffner
Millard Hurst Lambert, Iii
Patrick Reed Maloney
Michael Lawrence Sierra
Daniel David Sternbach
Marcos Luis Sznaidman
Timothy Mark Willson
Huaqiang Eric Xu
Françoise Jeanne GELLIBERT
Original Assignee
Glaxo Group Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to PL00353135A priority Critical patent/PL353135A1/xx
Priority to EP00943847A priority patent/EP1189895B8/fr
Application filed by Glaxo Group Limited filed Critical Glaxo Group Limited
Priority to US10/018,935 priority patent/US6710063B1/en
Priority to JP2001507012A priority patent/JP3490704B2/ja
Priority to BR0011891-5A priority patent/BR0011891A/pt
Priority to AT00943847T priority patent/ATE297384T1/de
Priority to DE60020701T priority patent/DE60020701T2/de
Priority to CA002377126A priority patent/CA2377126C/fr
Priority to DK00943847T priority patent/DK1189895T3/da
Priority to NZ515676A priority patent/NZ515676A/en
Priority to MXPA01013244A priority patent/MXPA01013244A/es
Priority to SI200030735T priority patent/SI1189895T1/sl
Priority to IL14663400A priority patent/IL146634A0/xx
Priority to AU58171/00A priority patent/AU765347B2/en
Publication of WO2001000603A1 publication Critical patent/WO2001000603A1/fr
Priority to IL146634A priority patent/IL146634A/en
Priority to NO20016078A priority patent/NO321872B1/no
Priority to HK02104378.2A priority patent/HK1042897B/zh

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D277/26—Radicals substituted by sulfur atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
    • A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D277/24—Radicals substituted by oxygen atoms

Definitions

  • the present invention relates to certain novel compounds.
  • the present invention relates to compounds that activate the delta subtype of the human peroxisome proliferator activated receptor ("hPPAR ⁇ ").
  • the present invention also relates to method for preparing and using the novel compounds and to methods for using activators of hPPAR ⁇ .
  • HMG CoA reductase inhibitors are useful for treating conditions characterized by high LDL-c levels. It has been shown that lowering LDL-c is not sufficient for reducing the risk of cardiovascular disease in some patients, particularly those with normal LDL-c levels. This population pool is identified by the independent risk factor of low
  • HDL-c The increased risk of cardiovascular disease associated with low HDL-c levels has not yet been successfully addressed by drug therapy (i.e. currently there are no drugs on the market that are useful for raising HDL-c) .
  • Syndrome X (including metabolic syndrome) is loosely defined as a collection of abnormalities including hyperinsulinemia, obesity, elevated levels of trigycerides, uric acid, fibrinogen, small dense LDL particles, and plasminogen activator inhibitor 1 (PAI-1), and decreased levels of HDL-c.
  • NIDDM non insulin dependent or Type 2 diabetes mellitus
  • ITT impaired glucose tolerance
  • PPAR-alpha Three mammalian Peroxisome Proliferator-Activated Receptors have been isolated and termed PPAR-alpha, PPAR-gamma, and PPAR-delta (also known as NUC1 or PPAR-beta). These PPARs regulate expression of target genes by binding to DNA sequence elements, termed PPAR response elements (PPRE).
  • PPRE PPAR response elements
  • PPRE's have been identified in the enhancers of a number of genes encoding proteins that regulate lipid metabolism suggesting that PPARs play a pivotal role in the adipogenic signaling cascade and lipid homeostasis (H. Keller and W. Wahli, Trends Endoodn. Met 291-296, 4 (1993)). It has now been reported that thiazolidinediones are potent and selective activators of PPAR-gamma and bind directly to the PPAR-gamma receptor (J.
  • Activators of the nuclear receptor PPAR ⁇ gamma have been shown in the clinic to enhance insulin-action, reduce serum glucose and have small but significant effects on reducing serum triglyceride levels in patients with Type 2 diabetes. See, for example, D. E. Kelly et al., Curr. Opin. Endocrinol. Diabetes, 90-96, 5 (2), (1998); M. D. Johnson et al., Ann. Pharmacother., 337-348, 32 (3), (1997); and M. repelnegger et al., Curr. Then Res., 403-416, 58 (7), (1997).
  • VLDL very low density lipoproteins
  • LPL liporotein lipase
  • Fibrates are a class of drugs which may lower serum triglycerides 20- 50%, lower LDLc 10-15%, shift the LDL particle size from the more atherogenic small dense to normal dense LDL, and increase HDLc 10-15%.
  • Experimental evidence indicates that the effects of fibrates on serum lipids are mediated through activation of PPAR ⁇ . See, for example, B. Staels et al., Curr. Pharm. Des., 1-14, 3 (1 ), (1997).
  • Activation of PPAR alpha results in transcription of enzymes that increase fatty acid catabolism and decrease de-novo fatty acid synthesis in the liver resulting in decreased triglyceride synthesis and VLDL production/secretion.
  • PPAR alpha activation decreases production of apoC-lll.
  • X represents a COOH (or a hydrolysable ester thereof) or tetrazole group
  • X 1 represents NH, NCH 3 , O, S, a bond (i.e. is absent), CH 2 , or CH where the dashed line indicates that when X 1 is CH the depicted bond is a double bond;
  • X 2 represents O or S
  • R 1 and R 2 independently represent H, CH 3 , OCH 3 , or halogen; n is 1 or 2; one of Y and Z is N and the other is S or O: y is O, 1 , 2, 3, 4 or 5;
  • Each R 3 independently represents CF 3 or halogen.
  • the present invention discloses a method for prevention or treatment of a human PPAR delta ("hPPAR ⁇ ”) mediated disease or condition comprising administration of a therapeutically effective amount of a compound of this invention.
  • hPPAR ⁇ mediated diseases or conditions include dyslipidemia including associated diabetic dyslipidemia and mixed dyslipidemia, syndrome X (as defined in this application this embraces metabolic syndrome), heart failure, hypercholesteremia, cardiovascular disease including atherosclerosis, arteriosclerosis, and hypertriglyceridemia, Type 2 diabetes mellitus, Type I diabetes, insulin resistance, hyperlipidemia, and regulation of appetite and food intake in subjects suffering from disorders such as obesity, anorexia bulimia, and anorexia nervosa.
  • the compounds of this invention are useful in the treatment and prevention of cardiovascular diseases and conditions including atherosclerosis, arteriosclerosis, hypertriglyceridemia, and mixed dyslipidaemia.
  • the present invention provides pharmaceutical compositions comprising a compound of the invention, preferably in association with a pharmaceutically acceptable diluent or carrier.
  • the present invention provides a compound of the invention for use in therapy, and in particular, in human medicine.
  • the present invention provides the use of a compound of the invention for the manufacture of a medicament for the treatment of a hPPAR ⁇ mediated disease or condition.
  • the present invention provides a method for lowering triglycerides by administration of a hPPAR ⁇ agonist.
  • a hPPAR ⁇ agonist is a selective agonist.
  • the present invention provides the use of a hPPAR ⁇ agonist for the manufacture of a medicament for lowering triglyceride levels.
  • the hPPAR ⁇ agonist is a selective agonist.
  • the present invention provides a method for treating Type 2 diabetes, decreasing insulin resistance or lowering blood pressure comprising administering a hPPAR ⁇ agonist.
  • a hPPAR ⁇ agonist is a selective agonist.
  • a hPPAR ⁇ agonist for the manufacture of a medicament for treating Type 2 diabetes, decreasing insulin resistance or lowering blood pressure.
  • the hPPAR ⁇ agonist is a selective agonist.
  • the invention provides a method for decreasing fibrinogen levels comprising administering a hPPAR ⁇ agonist.
  • the hPPAR ⁇ agonist is a selective agonist.
  • a hPPAR ⁇ agonist for the manufacture of a medicament for decreasing fibrinogen levels.
  • the hPPAR ⁇ agonist is a selective agonist.
  • the invention provides a method for decreasing LDLc levels comprising administering a hPPAR ⁇ agonist.
  • a hPPAR ⁇ agonist is a selective agonist.
  • the invention provides the use of a hPPAR ⁇ agonist for the manufacture of a medicament for decreasing LDLc levels.
  • a hPPAR ⁇ agonist is a selective agonist.
  • the invention provides a method for shifting the LDL particle size from small dense to normal dense LDL comprising administering a hPPAR ⁇ agonist.
  • the hPPAR ⁇ agonist is a selective agonist.
  • the invention provides the use of a hPPAR ⁇ agonist for the manufacture of a medicament for shifting the LDL particle size from small dense to normal dense LDL.
  • the hPPAR ⁇ agonist is a selective agonist.
  • a compound of the invention means a compound of formula (I) or a pharmaceutically acceptable salt or, solvate, thereof.
  • esters and tetrazole derivatives are included in the scope of this invention, the acids are preferred because the data suggests that while the esters are useful compounds, it may actually be the acids to which they hydrolyze that are the active compounds.
  • Esters that hydrolyze readily can produce the carboxylic acid in the assay conditions or in vivo. Generally the carboxylic acid is active in both the binding and transient transfection assays, while the ester does not usually bind well but is active in the transient transfection assay presumably due to hydrolysis.
  • Preferred hydrolysable esters are C ⁇ alkyl esters wherein the alkyl group may be straight chain or branched chain. Methyl or ethyl esters are more preferred.
  • X represents COOH
  • X 1 is O, S, or is absent. More preferably X 1 represents O.
  • X 2 is S.
  • R 1 is H or CH 3 , more preferably CH 3 .
  • R 2 is H.
  • Z is N.
  • Y is S.
  • n is 1.
  • y is 1 or 2.
  • one of the substituents is halogen; more preferably one is halogen and the other is CF 3 . More preferably y is 1.
  • y is 1 , preferably the substituent is in the para position on the ring and is more preferably CF 3 .
  • a particular group of compounds is compounds of formula (II), and pharmaceutically acceptable salts, solvates, and hydrolyzable esters thereof, wherein
  • X 1 is NH, NCH 3 , O, S, a bond (i.e. is absent), CH 2 , or CH where the dashed line indicates that when X 1 is CH the depicted bond is a double bond; X 2 is O or S;
  • R 1 is H, CH 3 , OCH 3 , or halogen
  • R 2 is H, OCH 3 , or halogen n is 1 or 2
  • one of Y and Z is N and the other is S or O
  • R 3 is H, CF 3 or halogen.
  • preferred compounds of this invention include those in which several or each variable in Formula (I) is selected from the preferred, more preferred, or most preferred groups for each variable.
  • this invention is intended to include all combinations of preferred, more preferred, and most preferred groups.
  • the compounds of formula (I) are hPPAR ⁇ agonists.
  • agonist or “activating compound”, or “activator”, or the like, is meant those compounds which have a pKi of at least 6.0, preferably at least 7.0, to the relevant PPAR, for example hPPAR ⁇ , in the binding assay described below, and which achieve at least 50% activation of the relevant PPAR relative to the appropriate indicated positive control in the transfection assay described below at concentrations of 10 '5 M or less.
  • the agonist of this invention achieve 50% activation of human PPAR ⁇ in the transfection assay at concentrations of 10 "7 M or less, more preferably 10 "9 M or less.
  • the compounds of formula (I) are selective hPPAR ⁇ agonists.
  • a "selective hPPAR ⁇ agonist” is a hPPAR ⁇ agonist whose EC50 for PPAR ⁇ is at least 10 fold lower than its EC50 for PPAR ⁇ and PPAR ⁇ . Such selective compounds may be referred to as "10-fold selective.”
  • EC50 is defined in the transfection assay described below and is the concentration at which a compound achieves 50% of its maximum activity. Most preferred compounds are greater than 100-fold selective hPPAR ⁇ agonists.
  • the PPAR ⁇ selective compounds of this invention elevate HDL-c in db/db mice and primate models and lower fibrinogen in primate models. These PPAR ⁇ selective agonists unexpectedly lower triglycerides and insulin levels in the primate.
  • Preferred compounds of the present invention include:
  • More preferred compounds of the invention are:
  • a particularly preferred compound of the invention is:
  • the compounds of the present invention may also be utilized in the form of a pharmaceutically acceptable salt or solvate thereof.
  • physiologically acceptable salts of the compounds of formula (I) include conventional salts formed from pharmaceutically acceptable inorganic or organic acids or bases as well as quaternary ammonium acid addition salts.
  • suitable acid salts include hydrochloric, hydrobromic, sulfuric, phosphoric, nitric, perchloric, fumaric, acetic, propionic, succinic, glycolic, formic, lactic, maleic, tartaric, citric, palmoic, malonic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicylic, fumaric, toluenesulfonic, methanesulfonic, naphthalene-2-sulfonic, benzenesulfonic hydroxynaphthoic, hydroiodic, malic, steroic, tannic and the like.
  • acids such as oxalic, while not in themselves pharmaceutically acceptable, may be useful in the preparation of salts useful as intermediates in obtaining the compounds of the invention and their pharmaceutically acceptable salts.
  • suitable basic salts include sodium, lithium, potassium, magnesium, aluminium, calcium, zinc, N.N'-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine, N-methylglucamine and procaine salts.
  • solvates For example, a complex with water is known as a "hydrate”.
  • Solvates of the compound of formula (I) are within the scope of the invention. References hereinafter to a compound according to the invention include both compounds of formula (I) and their pharmaceutically acceptable salts and solvates.
  • treatment extends to prophylaxis as well as the treatment of established diseases or symptoms.
  • amount of a compound of the invention required for use in treatment will vary with the nature of the condition being treated and the age and the condition of the patient and will be ultimately at the discretion of the attendant physician or veterinarian.
  • doses employed for adult human treatment will typically be in the range of 0.02-5000 mg per day, preferably 1-1500 mg per day.
  • the desired dose may conveniently be presented in a single dose or as divided doses administered at appropriate intervals, for example as two, three, four or more sub-doses per day.
  • the present invention further provides for a pharmaceutical formulation comprising a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof together with one or more pharmaceutically acceptable carriers therefor and, optionally, other therapeutic and/or prophylactic ingredients.
  • Formulations of the present invention include those especially formulated for oral, buccal, parenteral, transdermal, inhalation, intranasal, tra ⁇ smucosal, implant, or rectal administration, however, oral administration is preferred.
  • the formulation may take the form of tablets or lozenges formulated in conventional manner.
  • Tablets and capsules for oral administration may contain conventional excipients such as binding agents, (for example, syrup, acacia, gelatin, sorbitol, tragacanth, mucilage of starch or polyvinylpyrrolidone), fillers (for example, lactose, sugar, microcrystalline cellulose, maize-starch, calcium phosphate or sorbitol), lubricants (for example, magnesium stearate, stearic acid, talc, polyethylene glycol or silica), disintegrants (for example, potato starch or sodium starch glycollate) or wetting agents, such as sodium lauryl sulfate.
  • binding agents for example, syrup, acacia, gelatin, sorbitol, tragacanth, mucilage of starch or polyvinylpyrrolidone
  • fillers for example, lactose, sugar, microcrystalline cellulose, maize-starch, calcium phosphate or sorbitol
  • lubricants
  • the compounds of the present invention may be incorporated into oral liquid preparations such as aqueous or oily suspensions, solutions, emulsions, syrups or elixirs, for example.
  • formulations containing these compounds may be presented as a dry product for constitution with water or other suitable vehicle before use.
  • Such liquid preparations may contain conventional additives such as suspending agents such as sorbitol syrup, methyl cellulose, glucose/sugar syrup, gelatin, hydroxyethylcellulose, carboxymethyl cellulose, aluminum stearate gel or hydrogenated edible fats; emulsifying agents such as lecithin, sorbitan mono-oleate or acacia; non- aqueous vehicles (which may include edible oils) such as almond oil, fractionated coconut oil, oily esters, propylene glycol or ethyl alcohol; and preservatives such as methyl or propyl p-hydroxybenzoates or sorbic acid.
  • Such preparations may also be formulated as suppositories, e.g., containing conventional suppository bases such as cocoa butter or other glycerides.
  • formulations of the present invention may be formulated for parenteral administration by injection or continuous infusion.
  • Formulations for injection may take such forms as suspensions, solutions, or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents.
  • the active ingredient may be in powder form for constitution with a suitable vehicle (e.g., sterile, pyrogen-free water) before use.
  • the formulations according to the invention may also be formulated as a depot preparation. Such long acting formulations may be administered by implantation (for example, subcutaneously or intramuscularly) or by intramuscular injection. Accordingly, the compounds of the invention may be formulated with suitable polymeric or hydrophobic materials (as an emulsion in an acceptable oil, for example), ion exchange resins or as sparingly soluble derivatives as a sparingly soluble salt, for example.
  • the formulations according to the invention may contain between 0.1- 99% of the active ingredient, conveniently from 30-95% for tablets and capsules and 3-50% for liquid preparations.
  • the compound of formula (I) for use in the instant invention may be used in combination with other therapeutic agents for example, statins and/or other lipid lowering drugs for example MTP inhibitors and LDLR upregulators.
  • the compounds of the invention may also be used in combination with antidiabetic agents, e.g. metformin, sulfonylureas, or PPAR gamma, PPAR alpha and PPAR alpha/gamma agonists (for example thiazolidinediones such as e.g. Pioglitazone and Rosiglitazone).
  • the compounds may also be used in combination with antihypertensive agents such as angiotensin antagonists eg telmisartan, calcium channel antagonists eg lacidipine and ACE inhibitors eg enalapril .
  • antihypertensive agents such as angiotensin antagonists eg telmisartan, calcium channel antagonists eg lacidipine and ACE inhibitors eg enalapril .
  • the invention thus provides in a further aspect the use of a combination comprising a compound of formula (I) with a further therapeutic agent in the treatment of a hPPAR delta mediated disease.
  • the compounds of formula (I) When used in combination with other therapeutic agents, the compounds may be administered either sequentially or simultaneously by any convenient route.
  • compositions comprising a combination as defined above optimally together with a pharmaceutically acceptable carrier or excipient comprise a further aspect of the invention.
  • the individual components of such combinations may be administered either sequentially or simultaneously in separate or combined pharmaceutical formulations.
  • the two compounds When combined in the same formulation it will be appreciated that the two compounds must be stable and compatible with each other and the other components of the formulation and may be formulated for administration. When formulated separately they may be provided in any convenient formulation, conveniently in such a manner as are known for such compounds in the art.
  • each compound may differ from that when the compound is used alone.
  • Appropriate doses will be readily appreciated by those skilled in the art.
  • Compounds of this invention may be conveniently prepared by a general process wherein a moiety like A is coupled to an alcohol (B) using the Mitsunobu protocol (O. Mitsunobu, 1981 Synthesis, p 1 ) or by alkylation of A using a suitable non nucleophilic base such as K 2 CO 3 , Cs 2 CO 3 or NaH, with an alkyl halide (C).
  • this synthesis is preferably carried out with the acid group protected by R.
  • R is 1-6 alkyl which can be hydrolyzed off to give an acid of Formula (I), or if readily hydrolyzable, the resulting ester can be administered.
  • n is1
  • Y is S
  • Z is N
  • R 3 is para-CF 3
  • the tetrazole derivatives may be conveniently prepared by a general process wherein a moiety like D is coupled to an alcohol (B) using the Mitsunobu protocol (O. Mitsunobu, 1981 Synthesis, p 1 ), by alkylation of D using a suitable non nucleophilic base such as K 2 CO 3 , Cs 2 CO 3 or NaH, with an alkyl halide (C) or by coupling of a moiety like E with an alkyl halide (C) using a suitable non nucleophilic base such as NaOH.
  • a suitable non nucleophilic base such as K 2 CO 3 , Cs 2 CO 3 or NaH
  • n is1
  • Y is S
  • Z is N
  • R 3 is para-CF 3
  • reaction mixture was diluted with CH 2 CI 2 (120 mL) and washed with NaHCO 3 (sat.) (2 x 240 mL) and water (2 x 240 mL), dried, filtered and evaporated to afford intermediate 2 (8.0 g, 27 mmol, 90%) as a yellow solid.
  • reaction mixture was diluted with CH 2 CI 2 (40 mL) and washed with NaHCO 3 (sat.) (2 x 80 mL) and water (2 x 80 mL), dried, filtered and evaporated to afford intermediate 5 (2.8 g, 10 mmol, 100%) as a yellow solid.
  • N-Methylanisidine (2.0 g, 15 mmol),methyl bromoacetate (2.25 g, 15 mmol), DMAP (0.04 g, 2% by wt), and Net 3 (2.25 g, 15 mmol) in EtOH (50 mL) was refluxed for 1 h. The solvents were evaporated. The remaining residue was chromatographied on a silica gel column with 10% EtOAc in hexanes to afford the title compound (70%) as a yellow oil: NMR (DMSO-d6) ⁇ 2.97 (s, 3H), 3.66(s,
  • Methyl 2-(4-hydroxyphenoxy)acetate was treated with dimethyl thiocarbamoyl chloride as described in general procedure 5 to afford, after column chromatography (hexane: EtOAc, 4:1 ), (84 %) as a yellow oil.
  • the oil was refluxed in tetradecane as to afford after column chromatography (hexane:EtOAc, 4:1 ) the title compound (53 %) as a yellow oil.
  • Methyl 4-hydroxyphenylacetate was treated with dimethyl thiocarbamoyl chloride as described in general procedure 5 to afford, after column chromatography (hexane:EtOAc, 4:1 ) (90 %) a yellow solid.
  • the solid was refluxed in tetradecane to afford after column chromatography (hexane:EtOAc,
  • Methyl 3-methoxy-4-hydroxyphenylacetate was treated with dimethyl thiocarbamoyl chloride as described in general procedure 5 to afford, after column chromatography (hexane:EtOAc, 4:1 ), a brown oil (95 %). The oil was refluxed in tetradecane to afford after column chromatography (hexane:EtOAc, 4:1 ) compound the title compound (17 %) as a yellow oil.
  • Rf of starting alcohol in 3:1 hexanes/ethyl acetate is 0.25
  • Rf of chloride in 3:1 hexanes/ethyl acetate is 0.75
  • Example 1 was hydrolyzed as described in the general procedure 3 to afford the title compound (74 %) as a solid: mp 149 -150°C.
  • Example 3 was hydrolyzed as described in the general procedure 3 to afford the-title compound (72 %) as a solid: mp 172 -174°C.
  • Example 5 was hydrolyzed as described in the general procedure 3 to afford the title compound (73 %) as a solid: mp 150-152°C.
  • Example 7 3-[4-( ⁇ 4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-5- yl ⁇ methoxy)phenyl]propanoic acid
  • Example 7 was hydrolyzed as described in the general procedure 3. The crude material was crystallized from acetone: hexane to afford the title compound (85 %) as a white solid: mp 98-100°C.
  • Example 9 was hydrolyzed as described in the general procedure to afford the title compound (45 %) as a white solid: mp 142-147°C. HPLC showed one peak at 3.942 min.
  • Example 11 was hydrolyzed as described in the general procedure 3 to afford the title compound (43 %) as a white solid: mp 136-138°C.
  • Example 13 was hydrolyzed as described in general procedure 3 to afford the title compound (85 %) as a white solid: mp 128-130°C.
  • Example 15 was hydrolyzed as described in the general procedure 3 to afford the title compound (82 %) as a white solid: mp 134-135°C.
  • Example 17 was hydrolyzed as described in the general procedure. The crude material was crystallized from acetone:water to afford the title compound
  • Example 21 was hydrolyzed as described in the general procedure 3 to afford the title compound (92 %) as a white solid: mp 193°C. HPLC showed one peak at 3.689 min.
  • Example 23 was hydrolyzed as described in general procedure 3 to afford the title compound (67 %) as a solid: mp 162 -163°C.
  • Anal. Calcd. for C ManualH n NO 5 F 3 C, 60.69; H, 4.63; N, 3.22. Found: C,
  • Example 25 was hydrolyzed as described in general procedure 3. The crude material was crystallized from EtOAc:hexane to afford the title compound
  • Example 27 was hydrolyzed as described in the general procedure to afford the title compound (97 %) as white solid: mp 155-165°C. HPLC showed one peak at 3.579 min.
  • Example 29 was hydrolyzed as described in the general procedure 3. The crude material was crystallized from acetone:hexane to afford the title compound
  • Example 31 was hydrolyzed as described in general procedure 3. The crude material was crystallized from acetone:water to afford the title compound (97 %) as a white solid: mp 128-130°C
  • Example 33 was hydrolyzed as described in the general procedure 3 to afford the title compound (20%) as a yellow solid.
  • Example 35 was hydrolyzed as described in general procedure 3 to afford the title compound (90 %) as a white solid: mp 126-127°C
  • Example 37 was hydrolyzed as described in general procedure 3 to afford the title compound (45%) as a yellow solid: mp 124-126 C; 1 H-NMR (acetone-d6) ⁇ 2.47 (s, 3H), 3.09(s, 3H), 408(s, 2H),5.25 (s, 2H), 6.70(d, 2H),
  • Example 39 was hydrolyzed as described in general procedure 3 to afford the title compound (46 %) as white solid: mp 158-160°C
  • Example 41 was hydrolyzed as described in general procedure 3 to afford the title compound (68 %) as yellow solid: mp 131-133°C
  • Example 43 was hydrolyzed as described in general procedure 3 to give crude material, that was purified by flash column chromatography (CHCI 3 :MeOH, 9:1 ) and then crystallized from ether to afford the title compound (50 %) as a white solid: mp 138-140°C. HPLC showed one peak at 3.580 min. Calcd. Mass for C 20 H 16 NO 4 F 3 S: (M + 1 ) + : 424.0830. Found (H.R.M.S): 424.0821.
  • Example 45 was hydrolyzed as described in general procedure 3. The crude material was crystallized from MeOH:water to afford the title compound (90%) as a yellow solid: mp 136-137°C
  • Example 47 was hydrolyzed as described in general procedure 3 to afford the title compound (78 %) as white solid: mp 202-203°C
  • Example 49 was hydrolyzed as described in general procedure 3 to afford the title compound (73 %) as a white solid: mp 189-191 °C
  • Example 51 was hydrolyzed as described in general procedure 3 to afford the title compound (21 %) as white solid: mp 181-182°C Anal. Calcd. for C 21 H 18 NO 3 F 3 S 2 0.25 HCI: C, 54.52; H, 3.98; N, 3.03.
  • Example 53 was hydrolyzed as described in general procedure 3 to afford the title compound (64%) as a yellow solid: mp 174-176°C
  • Example 59 was hydrolyzed as described in the general procedure. The crude material was crystallized from acetone:hexane to afford the title compound (96%) as white solid:
  • Example 61 was hydrolyzed as described in general procedure 3. The crude material was crystallized from acetone:hexane to afford the title compound (50 %) as yellow solid: mp 190°C.
  • Anal. Calcd. for C 20 H 16 NO 3 F 3 S 2 C, 54.66; H, 3.67; N, 3.19; S, 14.59. Found: C, 54.45; H, 3.71 ; N, 3.02; S, 14.83.
  • Example 63 was hydrolyzed as described in general procedure 3. The crude material was crystallized from MeOH:water to afford the title compound (67 %) as white solid: mp 156-157°C
  • Example 65 was hydrolyzed as described in general procedure 3. The crude material was crystallized from MeOH:water to afford the title compound (60 %) as yellow solid: mp 139-141 °C
  • Example 68 was hydrolyzed as described in general procedure 3. The crude material was chromatographed C ⁇ CI ⁇ MeOH (85:15) to afford the title compound (59%) as white solid: mp >250°C.
  • Example 70 ethyl 2- 2-methyl-4-[( ⁇ 4-methyl-2-[4-chlorophenyl]-1,3-thiazol-5- yl ⁇ methyl)sulfanyl]phenoxy ⁇ acetate
  • Intermediate 48 and intermediate 54 were coupled as described for example 67.
  • the crude material was chromatographed petroleum ether/EtOAc (90:10) to afford the title compound (53%) as clear oil that solidified upon standing.
  • Example 70 was hydrolyzed as described in general procedure 3. The crude material was crystallized from acetonotrile to afford the title compound (73%) as a pale yellow solid: mp 109°C.
  • Example 72 was hydrolyzed as described in general procedure 3 to afford the title compound (73%) as yellow foam: mp 45-46°C.
  • Example 74 was hydrolyzed as described in general procedure 3. The crude material was precipitated from ether to afford the title compound (75%) as a white solid: mp 143°C. Anal. Calcd. for C 20 H 17 CI 2 NO 3 S 2 cramp0.2H 2 O: C, 52.03; H, 3.75; N, 3.03; S,
  • Example 76 was hydrolyzed as described in general procedure 3. The crude material was crystallized from acetonitrile to afford the title compound (77%) as yellow solid: mp 119°C. MS m/z 422 (M+1 )
  • Example 78 was hydrolyzed as described in general procedure 3. The crude material was precipitated from ether to afford the title compound (89%) as a white solid: mp 178°C.
  • Example 80 was hydrolyzed as described in general procedure 3. The crude material was precipitated from ether to afford the title compound (81 %) as a yellow foam: mp ⁇ 50°C.
  • PPAR ligand binding domain (LBD) was expressed in E. coli as polyHis tagged fusion proteins and purified. The LBD was then labeled with biotin and immobilized on streptavidin- modified scintillation proximity beads.
  • the ligand binding domains for murine and human PPAR ⁇ , PPAR ⁇ , and PPAR ⁇ were each fused to the yeast transcription factor GAL4 DNA binding domain.
  • CV-1 cells were transiently transfected with expression vectors for the respective PPAR chimera along with a reporter construct containing five copies of the GAL4 DNA binding site driving expression of secreted placental alkaline phosphatase (SPAP) and ⁇ -galactosidase. After 16 h, the medium was exchanged to DME medium supplemented with 10% delipidated fetal calf serum and the test compound at the appropriate concentration.
  • SFP placental alkaline phosphatase
  • the positive control in the hPPAR ⁇ and hPPAR ⁇ assays was 2-[4-(2-(3-(4-fluorophenyl)-1- heptylureido)ethyl)-phenoxy]-2-methylpropionic acid, which can be prepared as described in Brown, Peter J., et. al. Synthesis Issue 7, 778-782 (1997), or patent publication WO 9736579.
  • HDLc increased by more than 40% in each monkey at the 3 mg/kg dose.
  • NMR analysis of lipoprotein particle composition showed a shift in the LDLc composition to fewer and larger LDLc particles.
  • Serum TG concentrations decreased by more than 30% in each monkey.
  • Fasting insulin decreased by more than 20% in each monkey.
  • Serum fibrinogen concentrations decreased by 10-20%, with peak activity observed at doses of 0.3 and 1 mg/kg.

Abstract

La présente invention concerne des composés représentés par la formule (1). Ces composés comprennent des activateurs sélectifs des récepteurs PPAR delta humains. (I)
PCT/EP2000/005720 1999-06-25 2000-06-22 Derives de thiazol et d'oxazole et utilisation pharmaceutique de ceux-ci WO2001000603A1 (fr)

Priority Applications (17)

Application Number Priority Date Filing Date Title
IL14663400A IL146634A0 (en) 1999-06-25 2000-06-22 Thiazole and oxazole derivatives and their pharmaceutical use
CA002377126A CA2377126C (fr) 1999-06-25 2000-06-22 Derives de thiazol et d'oxazole et utilisation pharmaceutique de ceux-ci
US10/018,935 US6710063B1 (en) 1999-06-25 2000-06-22 Activators of PPAR delta
JP2001507012A JP3490704B2 (ja) 1999-06-25 2000-06-22 チアゾールおよびオキサゾール誘導体ならびにそれらの医薬的使用
BR0011891-5A BR0011891A (pt) 1999-06-25 2000-06-22 Composto, composição farmacêutica, uso de um composto, métodos para tratamento de uma doença ou condição mediada pelo hpparso , para diminuir triglicerìdios em um paciente, para tratar a diabete do tipo 2, diminuir a resistência à insulina ou abaixar a pressão sanguìnea em um paciente, para diminuir os nìveis de fribogênio em um paciente, para diminuir o ldlc em um paciente e para mudar o tamanho da partìcula do ldl denso pequeno para denso normal em um paciente, e , uso de uma agonista hpparso
AT00943847T ATE297384T1 (de) 1999-06-25 2000-06-22 Thiazol- und oxazol-derivate und ihre pharmazeutische verwendung
DE60020701T DE60020701T2 (de) 1999-06-25 2000-06-22 Thiazol- und oxazol-derivate und ihre pharmazeutische verwendung
PL00353135A PL353135A1 (en) 1999-06-25 2000-06-22 Thiazole and oxazole derivatives and their pharmaceutical use
DK00943847T DK1189895T3 (da) 1999-06-25 2000-06-22 Thiazol- og oxazolderivater og deres farmaceutiske anvendelse
MXPA01013244A MXPA01013244A (es) 1999-06-25 2000-06-22 Derivados de tiazol y oxazol y su uso farmaceutico.
NZ515676A NZ515676A (en) 1999-06-25 2000-06-22 Thiazole and oxazole derivatives and their pharmaceutical use
SI200030735T SI1189895T1 (sl) 1999-06-25 2000-06-22 Tiazolni in oksazolni derivati in njihova farmacevtska uporaba
EP00943847A EP1189895B8 (fr) 1999-06-25 2000-06-22 Derives de thiazol et d'oxazole et utilisation pharmaceutique de ceux-ci
AU58171/00A AU765347B2 (en) 1999-06-25 2000-06-22 Thiazole and oxazole derivatives and their pharmaceutical use
IL146634A IL146634A (en) 1999-06-25 2001-11-20 Thiazole and oxazole derivatives and their pharmaceutical use
NO20016078A NO321872B1 (no) 1999-06-25 2001-12-13 Tiazol- og oksazolderivater, samt anvendelse derav og farmasoytisk preparat.
HK02104378.2A HK1042897B (zh) 1999-06-25 2002-06-11 噻唑和噁唑衍生物及其藥物用途

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB9914977.5A GB9914977D0 (en) 1999-06-25 1999-06-25 Chemical compounds
GB9914977.5 1999-06-25

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US10/018,935 A-371-Of-International US6710063B1 (en) 1999-06-25 2000-06-22 Activators of PPAR delta
US10/383,011 Continuation US6723740B2 (en) 1999-06-25 2003-03-06 Activator of PPAR delta

Publications (1)

Publication Number Publication Date
WO2001000603A1 true WO2001000603A1 (fr) 2001-01-04

Family

ID=10856125

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2000/005720 WO2001000603A1 (fr) 1999-06-25 2000-06-22 Derives de thiazol et d'oxazole et utilisation pharmaceutique de ceux-ci

Country Status (29)

Country Link
US (2) US6710063B1 (fr)
EP (1) EP1189895B8 (fr)
JP (2) JP3490704B2 (fr)
KR (1) KR100668026B1 (fr)
CN (1) CN1164579C (fr)
AR (1) AR035320A1 (fr)
AT (1) ATE297384T1 (fr)
AU (1) AU765347B2 (fr)
BR (1) BR0011891A (fr)
CA (1) CA2377126C (fr)
CO (1) CO5180622A1 (fr)
CZ (1) CZ300654B6 (fr)
DE (1) DE60020701T2 (fr)
ES (1) ES2243276T3 (fr)
GB (1) GB9914977D0 (fr)
HK (1) HK1042897B (fr)
HU (1) HUP0201858A3 (fr)
IL (2) IL146634A0 (fr)
MX (1) MXPA01013244A (fr)
MY (1) MY120090A (fr)
NO (1) NO321872B1 (fr)
NZ (1) NZ515676A (fr)
PE (1) PE20010406A1 (fr)
PL (1) PL353135A1 (fr)
PT (1) PT1189895E (fr)
TR (1) TR200103612T2 (fr)
TW (1) TWI256389B (fr)
WO (1) WO2001000603A1 (fr)
ZA (1) ZA200109804B (fr)

Cited By (106)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002028433A2 (fr) * 2000-10-05 2002-04-11 Glaxo Group Limited Medicaments
WO2002028434A2 (fr) * 2000-10-05 2002-04-11 Glaxo Group Limited Medicaments
WO2002050048A1 (fr) * 2000-12-20 2002-06-27 Glaxo Group Limited Thiaoxazoles et oxazoles, utilisation de ces derniers en tant qu'activateurs des recepteurs humains actives par un proliferateur de peroxysomes
WO2002050047A1 (fr) * 2000-12-20 2002-06-27 Glaxo Group Limited Oxazoles et thiazoles substitues utiles en tant qu'agonistes de hppar alpha
WO2002059098A1 (fr) * 2000-12-20 2002-08-01 Glaxo Group Limited Derives de thiazole et d'oxazole en tant qu'activateurs de recepteurs actives par le proliferateur du peroxysome humain
WO2002062774A1 (fr) * 2000-12-20 2002-08-15 Glaxo Group Limited Derives thiazole destines au traitement de troubles associes a des recepteurs ppar
WO2002070011A2 (fr) * 2001-02-02 2002-09-12 Smithkline Beecham Corporation Regimes therapeutiques
WO2002076957A1 (fr) * 2001-03-23 2002-10-03 Nippon Chemiphar Co.,Ltd. Activateur de recepteur active par les proliferateurs du peroxysome
WO2002083131A1 (fr) * 2001-04-13 2002-10-24 The Regents Of The University Of California Activateurs et ligands de ppar-beta/delta destines au traitement d'affections de la peau
WO2002096895A1 (fr) * 2001-05-31 2002-12-05 Glaxo Group Limited Derives d'oxazol/de thiazol activateurs du recepteur du hppar alpha
WO2003016291A1 (fr) * 2001-08-10 2003-02-27 Nippon Chemiphar Co., Ltd. Activateur du recepteur $g(d) sensible au proliferateur de peroxysome
WO2003072100A1 (fr) * 2002-02-25 2003-09-04 Eli Lilly And Company Modulateurs du recepteur active du proliferateur des peroxysomes
WO2003072102A1 (fr) 2002-02-25 2003-09-04 Eli Lilly And Company Modulateurs des récepteurs activés par les proliférateurs de peroxisomes
WO2003074052A1 (fr) * 2002-03-07 2003-09-12 Warner-Lambert Company Llc Derives de thiazole et d'oxazole qui modulent l'activite du recepteur ppar
WO2003074504A2 (fr) * 2002-02-28 2003-09-12 Smithkline Beecham Corporation Procede de preparation de composes chimiques
WO2003074495A1 (fr) * 2002-03-01 2003-09-12 Smithkline Beecham Corporation Activateurs de hppars
WO2003074051A1 (fr) * 2002-03-07 2003-09-12 Warner-Lambert Company Llc Thiazoles et oxazoles substitues modulant l'activite de ppar
WO2003074050A1 (fr) * 2002-03-07 2003-09-12 Warner-Lambert Company Llc Derives de thiazole et d'oxazole qui modulent l'activite de ppar
WO2003084535A1 (fr) * 2002-04-05 2003-10-16 Warner-Lambert Company Llc Agents anti-diabetiques
WO2003099793A1 (fr) * 2002-05-24 2003-12-04 Takeda Pharmaceutical Company Limited Derives 1,2-azole presentant une activite hypoglycemique et hypolipidemique
WO2003106442A1 (fr) * 2002-05-04 2003-12-24 Heonjoong Kang Procede pour l'elaboration de derive thiazole et composes intermediaires a cet effet
WO2004005266A1 (fr) * 2002-07-03 2004-01-15 F. Hoffmann-La Roche Ag Derives oxazole et utilisation de ceux-ci en tant que sensibilisateurs a l'insuline
WO2004024705A1 (fr) * 2002-09-10 2004-03-25 Takeda Pharmaceutical Company Limited Composes heterocycliques a cinq elements
JP2004123732A (ja) * 2002-09-10 2004-04-22 Takeda Chem Ind Ltd ５員複素環化合物
WO2004037776A2 (fr) 2002-10-28 2004-05-06 Novo Nordisk A/S Nouveaux composes, leur preparation et leur utilisation
WO2004037775A1 (fr) 2002-10-28 2004-05-06 Novo Nordisk A/S Nouveaux composes traitant les maladies mediees par le ppar
EP1435946A2 (fr) * 2001-09-14 2004-07-14 Tularik Inc. Composes biaryles lies
WO2004063155A1 (fr) * 2003-01-06 2004-07-29 Eli Lilly And Company Derives heterocycliques fusionnes utilises en tant que modulateurs ppar
WO2004076447A1 (fr) * 2003-02-27 2004-09-10 Aventis Pharma Deutschland Gmbh Derives de cycloalkyles comportant des groupes acides carboxyliques bioisosteres, leur procede de production et leur utilisation en tant que medicaments
JP2004277397A (ja) * 2002-05-24 2004-10-07 Takeda Chem Ind Ltd １，２−アゾール誘導体
US6869967B2 (en) 2001-07-30 2005-03-22 Novo Nordisk A/S Peroxisome proliferator-activated receptor (PPAR) active vinyl carboxylic acid derivatives
WO2005028453A1 (fr) 2003-09-22 2005-03-31 Ono Pharmaceutical Co., Ltd. Derive d'acide phenylacetique, ainsi que procede de production et utilisation de celui-ci
US6875780B2 (en) 2002-04-05 2005-04-05 Warner-Lambert Company Compounds that modulate PPAR activity and methods for their preparation
US6890947B2 (en) 2002-09-12 2005-05-10 Hoffmann-La Roche Inc. Indolyl derivatives
EP1531810A2 (fr) * 2002-07-09 2005-05-25 Bristol-Myers Squibb Company Derives heterocycliques substitues utiles comme agents antidiabetique et anti-obesite et procede correspondant
WO2005060958A1 (fr) * 2003-12-19 2005-07-07 Kalypsys, Inc. Derives de l'acide (5- (2-phenyl)-thiazol-5-ylmethoxy)-indol-1-yl) -acetique et composes associes en tant que modulateurs du recepteur ppar-delta humain pour le traitement de troubles metaboliques tels que le diabete de type 2
WO2005097098A2 (fr) * 2004-04-01 2005-10-20 Aventis Pharmaceuticals Inc. Utilisation d'agonistes delta de recepteur active de la proliferation des peroxysomes destines au traitement de la sep et d'autres troubles de demyelinisation
WO2005097763A2 (fr) * 2004-04-01 2005-10-20 Aventis Pharmaceuticals Inc. 1,3,4-oxadiazol-2-ones en tant que modulateurs des ppar delta et leur utilisation
WO2005097762A2 (fr) * 2004-04-01 2005-10-20 Aventis Pharmaceuticals Inc. 1,3,4-oxadiazol-2-ones utilises en tant que modulateurs de ppar delta et utilisation associee
US6987118B2 (en) 2003-05-21 2006-01-17 Pfizer Inc. Tetrahydroisoquinoline derivatives as PPAR-alpha activators
JP2006502151A (ja) * 2002-08-30 2006-01-19 エフ．ホフマン−ラ　ロシュ　アーゲー ＰＰＡＲα及びＰＰＡＲγアゴニストとしての新規２−アリールチアゾール化合物
US7067530B2 (en) 2001-07-30 2006-06-27 Novo Nordisk A/S Compounds, their preparation and use
WO2006071103A1 (fr) * 2004-12-31 2006-07-06 Heonjoong Kang Composés de type organosélénium et applications
WO2006074797A1 (fr) * 2005-01-14 2006-07-20 Merck Patent Gmbh Derives d'acide 6-phenylhex-5-enoique, procedes de fabrication de ceux-ci, compositions pharmaceutiques contenant ces composes et utilisations therapeutiques
US7091245B2 (en) 2002-09-05 2006-08-15 Novo Novdisk A/S Compounds, their preparation and use
US7098228B2 (en) 2002-11-25 2006-08-29 Hoffmann-La Roche Inc. Indolyl derivatives
US7105551B2 (en) 2000-12-20 2006-09-12 Smithkline Beecham Corporation Thiazole derivatives for treating PPAR related disorders
US7129268B2 (en) 2002-10-28 2006-10-31 Novo Nordisk A/S Peroxisome proliferator activated receptor-active arylene acetic acid derivatives
WO2006126514A1 (fr) 2005-05-27 2006-11-30 Shionogi & Co., Ltd. Derive d'arylacetate ayant un squelette isoxazole
EP1737809A2 (fr) * 2004-02-27 2007-01-03 Amgen, Inc Composes, compositions pharmaceutiques et procedes d'utilisation dans le traitement de troubles metaboliques
US7162262B2 (en) 2002-09-23 2007-01-09 Telefonaktiebolaget Lm Ericsson (Publ) Methods, systems and computer program products for requesting received power levels based on received block error rates utilizing an anti-windup and/or emergency procedure
WO2007003581A1 (fr) 2005-06-30 2007-01-11 Novo Nordisk A/S Acides phénoxyacétiques en tant qu'activateurs de rapp-delta
WO2007039177A2 (fr) 2005-09-29 2007-04-12 Sanofi-Aventis Derives de phenyl-1,2,4-oxadiazolone : procedes de preparation et utilisation comme produits pharmaceutiques
US7220877B2 (en) 2001-10-17 2007-05-22 Novo Nordisk A/S Compounds, their preparation and use
US7229998B2 (en) 2000-12-20 2007-06-12 Smithkline Beecham Corporation Thiazole and oxazole derivatives as activators of human peroxisome proliferator activated receptors
US7244763B2 (en) 2003-04-17 2007-07-17 Warner Lambert Company Llc Compounds that modulate PPAR activity and methods of preparation
WO2006127503A3 (fr) * 2005-05-20 2007-08-30 Amgen Inc Composes, compositions pharmaceutiques et methodes d'utilisation de ces derniers dans le traitement des troubles du metabolisme
WO2007119887A1 (fr) 2006-04-18 2007-10-25 Nippon Chemiphar Co., Ltd. AGENT D'ACTIVATION DU RÉCEPTEUR δ ACTIVÉ PAR LES PROLIFÉRATEURS DES PEROXISOMES
WO2007127502A2 (fr) * 2006-01-10 2007-11-08 Smithkline Beecham Corporation Polymorphe
US7304062B2 (en) 2000-11-10 2007-12-04 Eli Lilly And Company Peroxisome proliferator activated receptor alpha agonists
WO2007141295A1 (fr) * 2006-06-08 2007-12-13 High Point Pharmaceuticals, Llc Procédé de préparation de dérivés acide phénoxyacétique
KR100797798B1 (ko) * 2005-02-25 2008-01-24 재단법인서울대학교산학협력재단 퍼록시솜 증식자 활성화 수용체 델타 리간드 티아졸 유도체및 그의 제조방법
EP1889613A1 (fr) * 2005-05-27 2008-02-20 Shionogi & Co., Ltd. Composition pharmaceutique comprenant de la vitamine k
EP1911462A2 (fr) 2001-01-26 2008-04-16 Schering Corporation Combinaisons comprenant un inhibiteur d'absorption de stérol
WO2008066356A1 (fr) 2006-12-02 2008-06-05 Seoul National University Industry Foundation Composés aryles en tant que ligands ppar et leur utilisation
US7396642B2 (en) 2001-07-17 2008-07-08 Teijin Limited Methods of screening for a compound that enhances thermogenesis
WO2008084962A1 (fr) * 2007-01-08 2008-07-17 Seoul National University Industry Foundation COMPOSÉ DE THIAZOLE LIGAND DU PPARδ ET PRÉPARATIONS PHARMACEUTIQUE, COSMÉTIQUE, ET BIOALIMENTAIRE LE CONTENANT
US7456218B2 (en) 2003-12-25 2008-11-25 Takeda Pharmaceutical Company Limited 3-(4-benzyloxyphenyl) propanoic acid derivatives
WO2008154023A1 (fr) * 2007-06-11 2008-12-18 Cerenis Therapeutics S.A. Nouvelles utilisations d'agonistes du ppar delta
WO2009030450A2 (fr) 2007-09-03 2009-03-12 Syngenta Limited Nouveaux herbicides
JP2009138011A (ja) * 2001-05-15 2009-06-25 F Hoffmann La Roche Ag 糖尿病の処置においてｐｐａｒ−アルファ及び−ガンマアクチベーターとして使用するためのカルボン酸置換オキサゾール誘導体
EP2083006A1 (fr) 2004-04-01 2009-07-29 Sanofi-Aventis Deutschland GmbH Oxadiazolones, leurs procédés de préparation et leur utilisant en tant que produits pharmaceutiques
US7572934B2 (en) 2007-04-16 2009-08-11 Amgen Inc. Substituted biphenyl GPR40 modulators
US7582803B2 (en) 2005-09-14 2009-09-01 Amgen Inc. Conformationally constrained 3-(4-hydroxy-phenyl)-substituted-propanoic acids useful for treating metabolic disorders
US7585880B2 (en) 2003-12-26 2009-09-08 Takeda Pharmaceutical Company Limited Phenylpropanoic acid derivatives
WO2009128558A1 (fr) 2008-04-15 2009-10-22 日本ケミファ株式会社 Activateur pour récepteur activé par les proliférateurs de peroxysomes
US20100021386A1 (en) * 2006-09-08 2010-01-28 De La Monte Suzanne Marie Treatment, prevention,and reversal of alcohol-induced liver disease
WO2010015212A1 (fr) 2008-08-07 2010-02-11 浙江海正药业股份有限公司 COMPOSÉ AVEC EFFET D’AGITATION SUR LE RÉCEPTEUR δ ACTIVÉ PAR LES PROLIFÉRATEURS DE PEROXISOME ET UTILISATION DE CELUI-CI
US7687526B2 (en) 2006-09-07 2010-03-30 Amgen Inc. Benzo-fused compounds for use in treating metabolic disorders
WO2010045361A1 (fr) 2008-10-17 2010-04-22 Metabolex, Inc. Procédés de réduction de petites particules denses de ldl
US7709528B2 (en) 2002-10-28 2010-05-04 High Point Pharmaceuticals, Llc Compounds, their preparation and use
US7714008B2 (en) 2006-09-07 2010-05-11 Amgen Inc. Heterocyclic GPR40 modulators
US7816385B2 (en) 2002-12-20 2010-10-19 High Point Pharmaceuticals, Llc Dimeric dicarboxylic acid derivatives, their preparation and use
US7851493B2 (en) 2005-09-29 2010-12-14 Sanofi-Aventis Phenyl-1,2,4-oxadiazolone derivatives with phenyl group, processes for their preparation and their use as pharmaceuticals
US7943613B2 (en) 2005-12-22 2011-05-17 High Point Pharmaceuticals, Llc Compounds, their preparation and use
US7943612B2 (en) 2006-03-09 2011-05-17 High Point Pharmaceuticals, Llc Compounds that modulate PPAR activity, their preparation and use
US7960369B2 (en) 2002-11-08 2011-06-14 Takeda Pharmaceutical Company Limited Receptor function regulator
US7968723B2 (en) 2004-05-05 2011-06-28 High Point Pharmaceuticals, Llc Compounds, their preparation and use
US8008525B2 (en) 2003-11-26 2011-08-30 Takeda Pharmaceutical Company Limited Receptor function regulating agent
US8030354B2 (en) 2007-10-10 2011-10-04 Amgen Inc. Substituted biphenyl GPR40 modulators
US8053598B2 (en) 2004-05-05 2011-11-08 High Point Pharmaceuticals, Llc Compounds, their preparation and use
US8106095B2 (en) 2003-09-19 2012-01-31 Janssen Pharmaceutica N.V. 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs
WO2012027331A1 (fr) 2010-08-27 2012-03-01 Ironwood Pharmaceuticals, Inc. Compositions et procédés pour traiter ou prévenir un syndrome métabolique et des maladies et troubles associés
US8242173B2 (en) 2004-09-15 2012-08-14 Janssen Pharmaceutica N.V. 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs
US8258177B2 (en) 2003-09-19 2012-09-04 Janssen Pharmaceutica, N.V. 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs
EP2527333A1 (fr) 2007-06-28 2012-11-28 Syngenta Limited Composés de pyrandione, thiopyrandione et cyclohexanetrione ayant des propriétés herbicides
US8450522B2 (en) 2008-03-06 2013-05-28 Amgen Inc. Conformationally constrained carboxylic acid derivatives useful for treating metabolic disorders
US8633184B2 (en) 2006-04-18 2014-01-21 Janssen Pharmaceutica N.V. Benzoazepin-oxy-acetic acid derivatives as PPAR-delta agonists used for the increase of HDL-C, lower LDL-C and lower cholesterol
US8669288B2 (en) 2005-09-14 2014-03-11 Janssen Pharmaceutica N.V. Lysine salts of 4-((phenoxyalkyl)thio)-phenoxyacetic acid derivatives
US8748462B2 (en) 2008-10-15 2014-06-10 Amgen Inc. Spirocyclic GPR40 modulators
US9192601B2 (en) 2006-12-29 2015-11-24 Salk Institute For Biological Studies Methods for enhancing muscle performance and tone
US10456406B2 (en) 2013-09-09 2019-10-29 Vtv Therapeutics Llc Use of a PPAR-δ agonist for reducing loss of muscle strength, muscle mass, or type I muscle fibers in an immobilized limb
EP3871667A4 (fr) * 2018-10-23 2022-08-17 Japan Science and Technology Agency Activateur de ppar?
WO2022189856A1 (fr) * 2021-03-08 2022-09-15 Abionyx Pharma Sa Composés utiles pour le traitement des maladies du foie
US11634387B2 (en) 2019-09-26 2023-04-25 Abionyx Pharma Sa Compounds useful for treating liver diseases
US11931365B2 (en) 2022-01-25 2024-03-19 Reneo Pharmaceuticals, Inc. Use of PPAR-delta agonists in the treatment of disease

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7148246B2 (en) * 2003-02-27 2006-12-12 Sanofi-Aventis Deutschland Gmbh Cycloalkyl derivatives having bioisosteric carboxylic acid groups, processes for their preparation and their use as pharmaceuticals
PE20060315A1 (es) * 2004-05-24 2006-05-15 Irm Llc Compuestos de tiazol como moduladores de ppar
ZA200610650B (en) * 2004-05-25 2009-04-29 Metabolex Inc Substituted triazoles as modulators of PPAR and methods of their preparation
JP2008500358A (ja) * 2004-05-25 2008-01-10 メタボレックス インコーポレーティッド Ｐｐａｒのモジュレーターとしての、二環式の置換されたトリアゾール、およびこれらの調製方法
JP2007269630A (ja) * 2004-06-23 2007-10-18 Toudai Tlo Ltd インスリン分泌促進剤
EP1812386A4 (fr) * 2004-10-22 2010-01-06 Seoul Nat Univ Ind Foundation Procede de preparation de derives de sulfure d'alkylaryle et nouveaux composes de sulfure
AP2007003979A0 (en) * 2004-11-23 2007-06-30 Warner Lambert Co 7-(2h-pyrazol-3-yl)-3,5-dihyroxy-heptanoic acid derivatives as hmg co-a reductase inhibitors for thetreatment of lipidemia
US20080051418A1 (en) * 2004-11-26 2008-02-28 Tsuyoshi Maekawa Arylalkanoic Acid Derivative
ES2379800T3 (es) * 2004-12-31 2012-05-03 Seoul National University Industry Foundation Compuestos con contenido en organoselenio su uso
WO2006121223A1 (fr) * 2005-05-07 2006-11-16 Heon Joong Kang Procede pour preparer des ligands de ppardelta et les composes intermediaires pour preparer ceux-ci
CN101007790B (zh) * 2006-01-27 2011-03-30 北京摩力克科技有限公司 草氨酸衍生物、其制备方法和医药用途
JP5301286B2 (ja) * 2006-02-03 2013-09-25 イーライ リリー アンド カンパニー Ｆｘ受容体を調節するための化合物及び方法
JP2009132620A (ja) * 2006-03-07 2009-06-18 Astellas Pharma Inc フェニルチアゾール誘導体
WO2007106469A2 (fr) * 2006-03-14 2007-09-20 Amgen Inc. Derives bicycliques de l'acide carboxylique utiles dans le traitement de troubles metaboliques
US20080004281A1 (en) * 2006-06-28 2008-01-03 Kalypsys, Inc. Methods for the modulation of crp by the selective modulation of ppar delta
WO2008016175A1 (fr) * 2006-08-03 2008-02-07 Nippon Chemiphar Co., Ltd. Agent activant de récepteur activé par les proliférateurs des peroxysomes
CA2663121C (fr) 2006-09-08 2016-01-19 Rhode Island Hospital Traitement, prevention et elimination d'une maladie cerebrale d'origine alcoolique
MX2009008923A (es) * 2007-02-22 2009-08-28 Irm Llc Compuestos y metodos para modular receptores acoplados por proteina g.
WO2009078981A2 (fr) * 2007-12-13 2009-06-25 Sri International Ligands ppar-delta et leurs procédés d'utilisation
EP2540711A4 (fr) * 2010-02-25 2014-01-22 Snu R&Db Foundation Dérivé de sélénazole ayant un ligand qui active le récepteur activé de la prolifération des peroxysomes (ppar), son procédé de préparation et utilisation des composés chimiques
CN102285933B (zh) * 2010-06-18 2016-03-09 浙江海正药业股份有限公司 一种对亚型过氧化物酶增殖物激活受体具有激动作用的化合物、其制备方法和应用
AU2011296737A1 (en) * 2010-08-31 2013-04-11 Snu R&Db Foundation Use of the fetal reprogramming of a PPAR delta agonist
US9695137B2 (en) * 2013-03-14 2017-07-04 The University Of Toledo Analogs of peroxisome proliferator activated receptor (PPAR) agonists, and methods of using the same
US10181018B2 (en) * 2013-03-14 2019-01-15 The University Of Toledo Analogs of proxisome proliferator activated receptor (PPAR) agonists and methods of using the same

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH08325250A (ja) * 1995-05-31 1996-12-10 Sumitomo Metal Ind Ltd 新規置換フェノール誘導体
WO1997028149A1 (fr) * 1996-02-02 1997-08-07 Merck & Co., Inc. Procede pour augmenter les niveaux de cholesterol hdl
WO1998007699A1 (fr) * 1996-08-19 1998-02-26 Japan Tobacco Inc. Derives d'acide propionique et applications de ces derives
US5847008A (en) * 1996-02-02 1998-12-08 Merck & Co., Inc. Method of treating diabetes and related disease states
US5859051A (en) * 1996-02-02 1999-01-12 Merck & Co., Inc. Antidiabetic agents
WO1999004815A1 (fr) * 1997-07-24 1999-02-04 Yamanouchi Pharmaceutical Co., Ltd. Compositions medicinales hypocholesterolemiantes
WO1999046232A1 (fr) * 1998-03-10 1999-09-16 Ono Pharmaceutical Co., Ltd. Derives d'acide carboxylique et medicaments contenant ces derives comme principe actif

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS644688A (en) * 1987-06-26 1989-01-09 Tokuyama Soda Kk Photochromic composition
JPH0793082B2 (ja) * 1987-09-07 1995-10-09 株式会社明電舎 真空インタラプタの化成方法
JP2551151B2 (ja) * 1989-06-22 1996-11-06 神鋼電機株式会社 潜熱回収方式の給湯装置における放熱装置
JP3039009B2 (ja) * 1991-06-25 2000-05-08 ソニー株式会社 固体撮像素子の駆動装置
TW268952B (fr) 1993-02-26 1996-01-21 Takeda Pharm Industry Co Ltd
JP3466273B2 (ja) 1993-06-11 2003-11-10 武田薬品工業株式会社 テトラゾール誘導体、その製造法およびそれを含んでなる医薬
US5591862A (en) * 1993-06-11 1997-01-07 Takeda Chemical Industries, Ltd. Tetrazole derivatives, their production and use
JP3836521B2 (ja) 1994-08-10 2006-10-25 武田薬品工業株式会社 ２，４−チアゾリジンジオン誘導体、その製造法およびそれを含んでなる医薬組成物
JP2850809B2 (ja) 1994-11-02 1999-01-27 武田薬品工業株式会社 ２，４−オキサゾリジンジオン誘導体およびそれを含んでなる医薬組成物
JP3880108B2 (ja) 1994-11-02 2007-02-14 武田薬品工業株式会社 ２，４−オキサゾリジンジオン誘導体、その製造法およびそれを含んでなる医薬組成物
JPH08325263A (ja) * 1995-05-31 1996-12-10 Sumitomo Metal Ind Ltd 新規２−アミノ−３−フェニルプロピオン酸誘導体
GB9604242D0 (en) * 1996-02-28 1996-05-01 Glaxo Wellcome Inc Chemical compounds
JP3215048B2 (ja) 1996-04-03 2001-10-02 日本たばこ産業株式会社 プロピオン酸誘導体及びその用途
KR102220553B1 (ko) * 2015-03-10 2021-02-26 한국전자통신연구원 표시 패널 및 그것을 포함하는 표시 장치

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH08325250A (ja) * 1995-05-31 1996-12-10 Sumitomo Metal Ind Ltd 新規置換フェノール誘導体
WO1997028149A1 (fr) * 1996-02-02 1997-08-07 Merck & Co., Inc. Procede pour augmenter les niveaux de cholesterol hdl
US5847008A (en) * 1996-02-02 1998-12-08 Merck & Co., Inc. Method of treating diabetes and related disease states
US5859051A (en) * 1996-02-02 1999-01-12 Merck & Co., Inc. Antidiabetic agents
WO1998007699A1 (fr) * 1996-08-19 1998-02-26 Japan Tobacco Inc. Derives d'acide propionique et applications de ces derives
WO1999004815A1 (fr) * 1997-07-24 1999-02-04 Yamanouchi Pharmaceutical Co., Ltd. Compositions medicinales hypocholesterolemiantes
EP1023907A1 (fr) * 1997-07-24 2000-08-02 Yamanouchi Pharmaceutical Co. Ltd. Compositions medicinales hypocholesterolemiantes
WO1999046232A1 (fr) * 1998-03-10 1999-09-16 Ono Pharmaceutical Co., Ltd. Derives d'acide carboxylique et medicaments contenant ces derives comme principe actif

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
H. SHINKAI ET AL., JOURNAL OF MEDICINAL CHEMISTRY, vol. 41, no. 11, 1998, pages 1927 - 33, XP002151949 *
PATENT ABSTRACTS OF JAPAN vol. 1997, no. 04 30 April 1997 (1997-04-30) *

Cited By (197)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002028434A3 (fr) * 2000-10-05 2002-08-15 Glaxo Group Ltd Medicaments
WO2002028434A2 (fr) * 2000-10-05 2002-04-11 Glaxo Group Limited Medicaments
US7084161B2 (en) 2000-10-05 2006-08-01 Smithklinebeecham Corporation Method for treating inflammatory diseases or conditions
WO2002028433A2 (fr) * 2000-10-05 2002-04-11 Glaxo Group Limited Medicaments
WO2002028433A3 (fr) * 2000-10-05 2002-08-15 Glaxo Group Ltd Medicaments
US7304062B2 (en) 2000-11-10 2007-12-04 Eli Lilly And Company Peroxisome proliferator activated receptor alpha agonists
US7196107B2 (en) 2000-12-20 2007-03-27 Smithkline Beecham Corporation Thia-and oxazoles and their use as ppars activators
WO2002062774A1 (fr) * 2000-12-20 2002-08-15 Glaxo Group Limited Derives thiazole destines au traitement de troubles associes a des recepteurs ppar
US7105551B2 (en) 2000-12-20 2006-09-12 Smithkline Beecham Corporation Thiazole derivatives for treating PPAR related disorders
US7091225B2 (en) 2000-12-20 2006-08-15 Smithkline Beecham Corporation Substituted oxazoles and thiazoles as hPPAR alpha agonists
WO2002050048A1 (fr) * 2000-12-20 2002-06-27 Glaxo Group Limited Thiaoxazoles et oxazoles, utilisation de ces derniers en tant qu'activateurs des recepteurs humains actives par un proliferateur de peroxysomes
US7439259B2 (en) * 2000-12-20 2008-10-21 Smithkline Beecham Corporation Thiazole derivatives for treating PPAR related disorders
AU2002246713B2 (en) * 2000-12-20 2004-09-09 Glaxo Group Limited Thiazole derivatives for treating PPAR related disorders
US7229998B2 (en) 2000-12-20 2007-06-12 Smithkline Beecham Corporation Thiazole and oxazole derivatives as activators of human peroxisome proliferator activated receptors
WO2002050047A1 (fr) * 2000-12-20 2002-06-27 Glaxo Group Limited Oxazoles et thiazoles substitues utiles en tant qu'agonistes de hppar alpha
WO2002059098A1 (fr) * 2000-12-20 2002-08-01 Glaxo Group Limited Derives de thiazole et d'oxazole en tant qu'activateurs de recepteurs actives par le proliferateur du peroxysome humain
US7449468B2 (en) 2000-12-20 2008-11-11 Smithkline Beecham Corporation Thiazole and oxazole derivatives as activators of human peroxisome proliferator activated receptors
EP1911462A2 (fr) 2001-01-26 2008-04-16 Schering Corporation Combinaisons comprenant un inhibiteur d'absorption de stérol
WO2002070011A3 (fr) * 2001-02-02 2003-04-24 Smithkline Beecham Corp Regimes therapeutiques
WO2002070011A2 (fr) * 2001-02-02 2002-09-12 Smithkline Beecham Corporation Regimes therapeutiques
WO2002076957A1 (fr) * 2001-03-23 2002-10-03 Nippon Chemiphar Co.,Ltd. Activateur de recepteur active par les proliferateurs du peroxysome
WO2002083131A1 (fr) * 2001-04-13 2002-10-24 The Regents Of The University Of California Activateurs et ligands de ppar-beta/delta destines au traitement d'affections de la peau
JP2009138011A (ja) * 2001-05-15 2009-06-25 F Hoffmann La Roche Ag 糖尿病の処置においてｐｐａｒ−アルファ及び−ガンマアクチベーターとして使用するためのカルボン酸置換オキサゾール誘導体
CN1307166C (zh) * 2001-05-31 2007-03-28 葛兰素集团有限公司 HPPAR－α受体的噁唑/噻唑衍生物活化剂
WO2002096895A1 (fr) * 2001-05-31 2002-12-05 Glaxo Group Limited Derives d'oxazol/de thiazol activateurs du recepteur du hppar alpha
KR100859591B1 (ko) * 2001-05-31 2008-09-23 글락소 그룹 리미티드 Ｈｐｐａｒ-알파 수용체의 옥사졸/티아졸-유도체 활성제
US7157479B2 (en) 2001-05-31 2007-01-02 Glaxo Group Limited Oxazol/thiazol-derivatives activators of the hPPAR-alpha receptor
US7396642B2 (en) 2001-07-17 2008-07-08 Teijin Limited Methods of screening for a compound that enhances thermogenesis
US6869967B2 (en) 2001-07-30 2005-03-22 Novo Nordisk A/S Peroxisome proliferator-activated receptor (PPAR) active vinyl carboxylic acid derivatives
US7067530B2 (en) 2001-07-30 2006-06-27 Novo Nordisk A/S Compounds, their preparation and use
WO2003016291A1 (fr) * 2001-08-10 2003-02-27 Nippon Chemiphar Co., Ltd. Activateur du recepteur $g(d) sensible au proliferateur de peroxysome
JP2009102442A (ja) * 2001-08-10 2009-05-14 Nippon Chemiphar Co Ltd ペルオキシソーム増殖剤応答性受容体δの活性化剤
US7265137B2 (en) 2001-08-10 2007-09-04 Nippon Chemiphar Co., Ltd. Activator of peroxisome proliferator-activated re-ceptor δ
KR100901683B1 (ko) * 2001-08-10 2009-06-08 닛뽕 케미파 가부시키가이샤 퍼옥시좀 증식제 응답성 수용체 δ의 활성화제
AU2002323776B2 (en) * 2001-08-10 2008-07-31 Nippon Chemiphar Co., Ltd. Activator for peroxisome proliferator-responsive receptor Delta
US7648999B2 (en) 2001-08-10 2010-01-19 Nippon Chemiphar Co., Ltd. Activator for peroxisome proliferator-activated receptor δ
US7652045B2 (en) 2001-08-10 2010-01-26 Nippon Chemiphar, Co., Ltd. Activator of peroxisome proliferator-activated receptor δ
JP2009280622A (ja) * 2001-08-10 2009-12-03 Nippon Chemiphar Co Ltd ペルオキシソーム増殖剤応答性受容体δの活性化剤
CN1330641C (zh) * 2001-08-10 2007-08-08 日本化学医药株式会社 过氧化物酶体增殖剂响应受体δ活化剂
US6869975B2 (en) 2001-09-14 2005-03-22 Tularik Inc. Linked biaryl compounds
EP1435946A2 (fr) * 2001-09-14 2004-07-14 Tularik Inc. Composes biaryles lies
US7645779B2 (en) 2001-09-14 2010-01-12 Amgen Inc. Linked biaryl compounds
EP1435946B1 (fr) * 2001-09-14 2013-11-06 Amgen Inc. Composes biaryles lies
US7220877B2 (en) 2001-10-17 2007-05-22 Novo Nordisk A/S Compounds, their preparation and use
WO2003072102A1 (fr) 2002-02-25 2003-09-04 Eli Lilly And Company Modulateurs des récepteurs activés par les proliférateurs de peroxisomes
US7259175B2 (en) 2002-02-25 2007-08-21 Eli Lilly And Company Peroxisome proliferator activated receptor modulators
US7153878B2 (en) 2002-02-25 2006-12-26 Eli Lilly And Company Peroxisome proliferator activated receptor modulators
WO2003072100A1 (fr) * 2002-02-25 2003-09-04 Eli Lilly And Company Modulateurs du recepteur active du proliferateur des peroxysomes
WO2003074504A2 (fr) * 2002-02-28 2003-09-12 Smithkline Beecham Corporation Procede de preparation de composes chimiques
WO2003074504A3 (fr) * 2002-02-28 2003-12-18 Smithkline Beecham Corp Procede de preparation de composes chimiques
WO2003074495A1 (fr) * 2002-03-01 2003-09-12 Smithkline Beecham Corporation Activateurs de hppars
US7319104B2 (en) 2002-03-01 2008-01-15 Smithkline Beecham Corporation hPPARs activators
WO2003074051A1 (fr) * 2002-03-07 2003-09-12 Warner-Lambert Company Llc Thiazoles et oxazoles substitues modulant l'activite de ppar
US6833380B2 (en) 2002-03-07 2004-12-21 Warner-Lambert Company, Llc Compounds that modulate PPAR activity and methods of preparation
US7109222B2 (en) 2002-03-07 2006-09-19 Warner-Lambert Company, Llc Compounds that modulate PPAR activity and methods of preparation
US6867224B2 (en) 2002-03-07 2005-03-15 Warner-Lambert Company Compounds that modulate PPAR activity and methods of preparation
WO2003074052A1 (fr) * 2002-03-07 2003-09-12 Warner-Lambert Company Llc Derives de thiazole et d'oxazole qui modulent l'activite du recepteur ppar
WO2003074050A1 (fr) * 2002-03-07 2003-09-12 Warner-Lambert Company Llc Derives de thiazole et d'oxazole qui modulent l'activite de ppar
USRE39916E1 (en) 2002-04-05 2007-11-06 Warner Lambert Company Compounds that modulate PPAR activity and methods for their preparation
US6939875B2 (en) 2002-04-05 2005-09-06 Warner-Lambert Company Compounds that modulate PPAR activity and methods for their preparation
US6875780B2 (en) 2002-04-05 2005-04-05 Warner-Lambert Company Compounds that modulate PPAR activity and methods for their preparation
US6964983B2 (en) 2002-04-05 2005-11-15 Warner-Lambert Company, Llc Compounds that modulate PPAR activity and methods for their preparation
WO2003084535A1 (fr) * 2002-04-05 2003-10-16 Warner-Lambert Company Llc Agents anti-diabetiques
US6716842B2 (en) 2002-04-05 2004-04-06 Warner-Lambert Company, Llc Antidiabetic agents
KR100474202B1 (ko) * 2002-05-04 2005-03-08 강헌중 티아졸 유도체의 제조방법 및 이를 제조하기 위한 중간체
US7241901B2 (en) 2002-05-04 2007-07-10 Heonjoong Kang Process for preparing thiazole derivative and the intermediate compounds for preparing the same
WO2003106442A1 (fr) * 2002-05-04 2003-12-24 Heonjoong Kang Procede pour l'elaboration de derive thiazole et composes intermediaires a cet effet
JP2005536480A (ja) * 2002-05-04 2005-12-02 カン，ヘンジョン チアゾール誘導体の製造方法及びこれを製造するための中間体
CN100457744C (zh) * 2002-05-04 2009-02-04 财团法人首尔大学校产学协力财团 噻唑衍生物的制备方法和用于制备噻唑衍生物的中间体化合物
JP2004277397A (ja) * 2002-05-24 2004-10-07 Takeda Chem Ind Ltd １，２−アゾール誘導体
WO2003099793A1 (fr) * 2002-05-24 2003-12-04 Takeda Pharmaceutical Company Limited Derives 1,2-azole presentant une activite hypoglycemique et hypolipidemique
CN100402510C (zh) * 2002-07-03 2008-07-16 霍夫曼-拉罗奇有限公司 噁唑衍生物及其作为胰岛素敏化剂的应用
WO2004005266A1 (fr) * 2002-07-03 2004-01-15 F. Hoffmann-La Roche Ag Derives oxazole et utilisation de ceux-ci en tant que sensibilisateurs a l'insuline
US7507757B2 (en) 2002-07-09 2009-03-24 Bristol-Myers Squibb Company Substituted heterocyclic derivatives useful as antidiabetic and antiobesity agents and method
EP1531810A4 (fr) * 2002-07-09 2008-05-28 Bristol Myers Squibb Co Derives heterocycliques substitues utiles comme agents antidiabetique et anti-obesite et procede correspondant
EP1531810A2 (fr) * 2002-07-09 2005-05-25 Bristol-Myers Squibb Company Derives heterocycliques substitues utiles comme agents antidiabetique et anti-obesite et procede correspondant
JP2006502151A (ja) * 2002-08-30 2006-01-19 エフ．ホフマン−ラ　ロシュ　アーゲー ＰＰＡＲα及びＰＰＡＲγアゴニストとしての新規２−アリールチアゾール化合物
US7091245B2 (en) 2002-09-05 2006-08-15 Novo Novdisk A/S Compounds, their preparation and use
WO2004024705A1 (fr) * 2002-09-10 2004-03-25 Takeda Pharmaceutical Company Limited Composes heterocycliques a cinq elements
US7368578B2 (en) 2002-09-10 2008-05-06 Takeda Pharmaceutical Company Limited Five-membered heterocyclic compounds
JP2004123732A (ja) * 2002-09-10 2004-04-22 Takeda Chem Ind Ltd ５員複素環化合物
US6890947B2 (en) 2002-09-12 2005-05-10 Hoffmann-La Roche Inc. Indolyl derivatives
US7162262B2 (en) 2002-09-23 2007-01-09 Telefonaktiebolaget Lm Ericsson (Publ) Methods, systems and computer program products for requesting received power levels based on received block error rates utilizing an anti-windup and/or emergency procedure
US7129268B2 (en) 2002-10-28 2006-10-31 Novo Nordisk A/S Peroxisome proliferator activated receptor-active arylene acetic acid derivatives
WO2004037775A1 (fr) 2002-10-28 2004-05-06 Novo Nordisk A/S Nouveaux composes traitant les maladies mediees par le ppar
WO2004037776A2 (fr) 2002-10-28 2004-05-06 Novo Nordisk A/S Nouveaux composes, leur preparation et leur utilisation
US7709528B2 (en) 2002-10-28 2010-05-04 High Point Pharmaceuticals, Llc Compounds, their preparation and use
US7960369B2 (en) 2002-11-08 2011-06-14 Takeda Pharmaceutical Company Limited Receptor function regulator
US7098228B2 (en) 2002-11-25 2006-08-29 Hoffmann-La Roche Inc. Indolyl derivatives
US7816385B2 (en) 2002-12-20 2010-10-19 High Point Pharmaceuticals, Llc Dimeric dicarboxylic acid derivatives, their preparation and use
US7598266B2 (en) 2003-01-06 2009-10-06 Eli Lilly And Company Fused heterocyclic derivatives as PPAR modulators
WO2004063155A1 (fr) * 2003-01-06 2004-07-29 Eli Lilly And Company Derives heterocycliques fusionnes utilises en tant que modulateurs ppar
US7384965B2 (en) 2003-01-06 2008-06-10 Eli Lilly And Company Fused heterocyclic derivatives as PPAR modulators
CN100398537C (zh) * 2003-02-27 2008-07-02 塞诺菲-安万特德国有限公司 包含生物等排性羧酸基团的环烷基衍生物、其制备方法以及其作为药物的用途
WO2004076447A1 (fr) * 2003-02-27 2004-09-10 Aventis Pharma Deutschland Gmbh Derives de cycloalkyles comportant des groupes acides carboxyliques bioisosteres, leur procede de production et leur utilisation en tant que medicaments
US7244763B2 (en) 2003-04-17 2007-07-17 Warner Lambert Company Llc Compounds that modulate PPAR activity and methods of preparation
US6987118B2 (en) 2003-05-21 2006-01-17 Pfizer Inc. Tetrahydroisoquinoline derivatives as PPAR-alpha activators
US8106095B2 (en) 2003-09-19 2012-01-31 Janssen Pharmaceutica N.V. 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs
US8258177B2 (en) 2003-09-19 2012-09-04 Janssen Pharmaceutica, N.V. 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs
US8450371B2 (en) 2003-09-19 2013-05-28 Janssen Pharmaceutica, N.V. 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs
US8518997B2 (en) 2003-09-19 2013-08-27 Janssen Pharmaceutica N.V. 4-(phenoxyalkyl)thio)-phenoxyacetic acids and analogs
US9724322B2 (en) 2003-09-19 2017-08-08 Janssen Pharmaceutica N.V. 4-(phenoxyalkyl)thio)-phenoxyacetic acids and analogs
WO2005028453A1 (fr) 2003-09-22 2005-03-31 Ono Pharmaceutical Co., Ltd. Derive d'acide phenylacetique, ainsi que procede de production et utilisation de celui-ci
US8008525B2 (en) 2003-11-26 2011-08-30 Takeda Pharmaceutical Company Limited Receptor function regulating agent
WO2005060958A1 (fr) * 2003-12-19 2005-07-07 Kalypsys, Inc. Derives de l'acide (5- (2-phenyl)-thiazol-5-ylmethoxy)-indol-1-yl) -acetique et composes associes en tant que modulateurs du recepteur ppar-delta humain pour le traitement de troubles metaboliques tels que le diabete de type 2
US7456218B2 (en) 2003-12-25 2008-11-25 Takeda Pharmaceutical Company Limited 3-(4-benzyloxyphenyl) propanoic acid derivatives
US7585880B2 (en) 2003-12-26 2009-09-08 Takeda Pharmaceutical Company Limited Phenylpropanoic acid derivatives
US7816367B2 (en) 2004-02-27 2010-10-19 Amgen Inc. Compounds, pharmaceutical compositions and methods for use in treating metabolic disorders
EP1737809A2 (fr) * 2004-02-27 2007-01-03 Amgen, Inc Composes, compositions pharmaceutiques et procedes d'utilisation dans le traitement de troubles metaboliques
EP1737809A4 (fr) * 2004-02-27 2007-10-17 Amgen Inc Composes, compositions pharmaceutiques et procedes d'utilisation dans le traitement de troubles metaboliques
US7649110B2 (en) 2004-02-27 2010-01-19 Amgen Inc. Compounds, pharmaceutical compositions and methods for use in treating metabolic disorders
WO2005097763A2 (fr) * 2004-04-01 2005-10-20 Aventis Pharmaceuticals Inc. 1,3,4-oxadiazol-2-ones en tant que modulateurs des ppar delta et leur utilisation
US7872032B2 (en) 2004-04-01 2011-01-18 Aventis Parmaceuticals Inc. 1, 3, 4-oxadiazol-2-ones as PPAR delta modulators and their use thereof
WO2005097098A3 (fr) * 2004-04-01 2005-12-22 Aventis Pharma Inc Utilisation d'agonistes delta de recepteur active de la proliferation des peroxysomes destines au traitement de la sep et d'autres troubles de demyelinisation
WO2005097762A3 (fr) * 2004-04-01 2005-12-15 Aventis Pharma Inc 1,3,4-oxadiazol-2-ones utilises en tant que modulateurs de ppar delta et utilisation associee
WO2005097763A3 (fr) * 2004-04-01 2005-12-15 Aventis Pharma Inc 1,3,4-oxadiazol-2-ones en tant que modulateurs des ppar delta et leur utilisation
WO2005097762A2 (fr) * 2004-04-01 2005-10-20 Aventis Pharmaceuticals Inc. 1,3,4-oxadiazol-2-ones utilises en tant que modulateurs de ppar delta et utilisation associee
US7638539B2 (en) 2004-04-01 2009-12-29 Aventis Pharmaceuticals Inc. 1, 3, 4-oxadiazol-2-ones as peroxisome-proliferator activated receptor delta modulators and their use in the treatment of neurological and metabolic disease
EP2083006A1 (fr) 2004-04-01 2009-07-29 Sanofi-Aventis Deutschland GmbH Oxadiazolones, leurs procédés de préparation et leur utilisant en tant que produits pharmaceutiques
WO2005097098A2 (fr) * 2004-04-01 2005-10-20 Aventis Pharmaceuticals Inc. Utilisation d'agonistes delta de recepteur active de la proliferation des peroxysomes destines au traitement de la sep et d'autres troubles de demyelinisation
US7576109B2 (en) 2004-04-01 2009-08-18 Aventis Pharmaceuticals Inc. 1,3,4-oxadiazol-2-ones as PPAR delta modulators and their use thereof
US8053598B2 (en) 2004-05-05 2011-11-08 High Point Pharmaceuticals, Llc Compounds, their preparation and use
US7968723B2 (en) 2004-05-05 2011-06-28 High Point Pharmaceuticals, Llc Compounds, their preparation and use
US8242173B2 (en) 2004-09-15 2012-08-14 Janssen Pharmaceutica N.V. 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs
EP1841748A4 (fr) * 2004-12-31 2010-01-06 Seoul Nat Univ Ind Foundation Composés de type organosélénium et applications
WO2006071103A1 (fr) * 2004-12-31 2006-07-06 Heonjoong Kang Composés de type organosélénium et applications
EP1841748A1 (fr) * 2004-12-31 2007-10-10 Kang, Heonjoong Composés de type organosélénium et applications
FR2880886A1 (fr) * 2005-01-14 2006-07-21 Merck Sante Soc Par Actions Si Derives de l'acide 6-phenylhex-5-enoique, procedes pour leur preparation, compositions pharmaceutiques les contenant et applications en therapeutique
WO2006074797A1 (fr) * 2005-01-14 2006-07-20 Merck Patent Gmbh Derives d'acide 6-phenylhex-5-enoique, procedes de fabrication de ceux-ci, compositions pharmaceutiques contenant ces composes et utilisations therapeutiques
KR100797798B1 (ko) * 2005-02-25 2008-01-24 재단법인서울대학교산학협력재단 퍼록시솜 증식자 활성화 수용체 델타 리간드 티아졸 유도체및 그의 제조방법
WO2006127503A3 (fr) * 2005-05-20 2007-08-30 Amgen Inc Composes, compositions pharmaceutiques et methodes d'utilisation de ces derniers dans le traitement des troubles du metabolisme
US7465804B2 (en) 2005-05-20 2008-12-16 Amgen Inc. Compounds, pharmaceutical compositions and methods for their use in treating metabolic disorders
US7781469B2 (en) 2005-05-27 2010-08-24 Shionogi & Co., Ltd. Arylacetate derivatives having isoxazole skeleton
EP1889613A1 (fr) * 2005-05-27 2008-02-20 Shionogi & Co., Ltd. Composition pharmaceutique comprenant de la vitamine k
EP1889613A4 (fr) * 2005-05-27 2010-11-24 Shionogi & Co Composition pharmaceutique comprenant de la vitamine k
WO2006126514A1 (fr) 2005-05-27 2006-11-30 Shionogi & Co., Ltd. Derive d'arylacetate ayant un squelette isoxazole
US8217086B2 (en) 2005-06-30 2012-07-10 High Point Pharmaceuticals, Llc Phenoxy acetic acids as PPAR delta activators
US7943669B2 (en) 2005-06-30 2011-05-17 High Point Pharmaceuticals, Llc Phenoxy acetic acids as PPAR delta activators
WO2007003581A1 (fr) 2005-06-30 2007-01-11 Novo Nordisk A/S Acides phénoxyacétiques en tant qu'activateurs de rapp-delta
US8426473B2 (en) 2005-06-30 2013-04-23 High Point Pharnaceuticals, LLC Phenoxy acetic acids as PPAR delta activators
EP2298742A1 (fr) 2005-06-30 2011-03-23 High Point Pharmaceuticals, LLC Acides phénoxyacétiques en tant qu'activateurs PPAR delta
US7582803B2 (en) 2005-09-14 2009-09-01 Amgen Inc. Conformationally constrained 3-(4-hydroxy-phenyl)-substituted-propanoic acids useful for treating metabolic disorders
US8669288B2 (en) 2005-09-14 2014-03-11 Janssen Pharmaceutica N.V. Lysine salts of 4-((phenoxyalkyl)thio)-phenoxyacetic acid derivatives
US7709481B2 (en) 2005-09-29 2010-05-04 Sanofi-Aventis Phenyl-1,2,4-oxadiazolone derivatives, processes for their preparation and methods for their use as pharmaceuticals
WO2007039177A2 (fr) 2005-09-29 2007-04-12 Sanofi-Aventis Derives de phenyl-1,2,4-oxadiazolone : procedes de preparation et utilisation comme produits pharmaceutiques
US7851493B2 (en) 2005-09-29 2010-12-14 Sanofi-Aventis Phenyl-1,2,4-oxadiazolone derivatives with phenyl group, processes for their preparation and their use as pharmaceuticals
US11420929B2 (en) 2005-12-22 2022-08-23 Vtv Therapeutics Llc Phenoxy acetic acids and phenyl propionic acids as PPAR delta agonists
US8362016B2 (en) 2005-12-22 2013-01-29 High Point Pharmaceuticals, Llc Phenyl propionic acids as PPAR delta activators
US7943613B2 (en) 2005-12-22 2011-05-17 High Point Pharmaceuticals, Llc Compounds, their preparation and use
US10947180B2 (en) 2005-12-22 2021-03-16 Vtv Therapeutics Llc Phenoxy acetic acids and phenyl propionic acids as PPAR delta agonists
US10471066B2 (en) 2005-12-22 2019-11-12 Vtv Therapeutics Llc Phenoxy acetic acids and phenyl propionic acids as PPAR delta agonists
US9663481B2 (en) 2005-12-22 2017-05-30 Vtv Therapeutics Llc Phenoxy acetic acids and phenyl propionic acids as PPARδ agonists
US9855274B2 (en) 2005-12-22 2018-01-02 Vtv Therapeutics Llc Phenoxy acetic acids and phenyl propionic acids as PPAR delta agonists
EP2386540A1 (fr) 2005-12-22 2011-11-16 High Point Pharmaceuticals, LLC Nouveaux composés, leur utilisation et préparation
WO2007127502A2 (fr) * 2006-01-10 2007-11-08 Smithkline Beecham Corporation Polymorphe
WO2007127502A3 (fr) * 2006-01-10 2008-01-03 Smithkline Beecham Corp Polymorphe
US7943612B2 (en) 2006-03-09 2011-05-17 High Point Pharmaceuticals, Llc Compounds that modulate PPAR activity, their preparation and use
US8633184B2 (en) 2006-04-18 2014-01-21 Janssen Pharmaceutica N.V. Benzoazepin-oxy-acetic acid derivatives as PPAR-delta agonists used for the increase of HDL-C, lower LDL-C and lower cholesterol
US8404726B2 (en) * 2006-04-18 2013-03-26 Nippon Chemiphar Co. Ltd. Activating agent for peroxisome proliferator activated receptor δ
NO341476B1 (no) * 2006-04-18 2017-11-27 Nippon Chemiphar Co Aktiveringsmiddel for proksisomproliferatoraktivert reseptor 
CN102643248A (zh) * 2006-04-18 2012-08-22 日本化学医药株式会社 过氧化物酶体增殖剂激活受体δ的激活剂
WO2007119887A1 (fr) 2006-04-18 2007-10-25 Nippon Chemiphar Co., Ltd. AGENT D'ACTIVATION DU RÉCEPTEUR δ ACTIVÉ PAR LES PROLIFÉRATEURS DES PEROXISOMES
WO2007141295A1 (fr) * 2006-06-08 2007-12-13 High Point Pharmaceuticals, Llc Procédé de préparation de dérivés acide phénoxyacétique
US7687526B2 (en) 2006-09-07 2010-03-30 Amgen Inc. Benzo-fused compounds for use in treating metabolic disorders
US8003648B2 (en) 2006-09-07 2011-08-23 Amgen Inc. Heterocyclic GPR40 modulators
US7714008B2 (en) 2006-09-07 2010-05-11 Amgen Inc. Heterocyclic GPR40 modulators
US9717719B2 (en) * 2006-09-08 2017-08-01 Rhode Island Hospital Treatment, prevention, and reversal of alcohol-induced liver disease
US20100021386A1 (en) * 2006-09-08 2010-01-28 De La Monte Suzanne Marie Treatment, prevention,and reversal of alcohol-induced liver disease
US8519145B2 (en) 2006-12-02 2013-08-27 Seoul National University Industry Foundation Aryl compounds as PPAR ligands and their use
WO2008066356A1 (fr) 2006-12-02 2008-06-05 Seoul National University Industry Foundation Composés aryles en tant que ligands ppar et leur utilisation
US9192601B2 (en) 2006-12-29 2015-11-24 Salk Institute For Biological Studies Methods for enhancing muscle performance and tone
KR100954237B1 (ko) 2007-01-08 2010-04-21 재단법인서울대학교산학협력재단 퍼록시솜 증식자 활성화 수용체 델타 리간드 티아졸 화합물및 이를 함유하는 의약, 화장품 및 건강식품 조성물
US8431715B2 (en) 2007-01-08 2013-04-30 Seoul National University Industry Foundation Thiazole compound (as PPARδ) ligand and pharmaceutical, cosmetic and health food comprised thereof
WO2008084962A1 (fr) * 2007-01-08 2008-07-17 Seoul National University Industry Foundation COMPOSÉ DE THIAZOLE LIGAND DU PPARδ ET PRÉPARATIONS PHARMACEUTIQUE, COSMÉTIQUE, ET BIOALIMENTAIRE LE CONTENANT
US8236831B2 (en) 2007-01-08 2012-08-07 Seoul National University Industry Foundation Thiazole compound (as PPARδ) ligand and pharmaceutical, cosmetic and health food comprised thereof
US7572934B2 (en) 2007-04-16 2009-08-11 Amgen Inc. Substituted biphenyl GPR40 modulators
WO2008154023A1 (fr) * 2007-06-11 2008-12-18 Cerenis Therapeutics S.A. Nouvelles utilisations d'agonistes du ppar delta
EP2527333A1 (fr) 2007-06-28 2012-11-28 Syngenta Limited Composés de pyrandione, thiopyrandione et cyclohexanetrione ayant des propriétés herbicides
WO2009030450A2 (fr) 2007-09-03 2009-03-12 Syngenta Limited Nouveaux herbicides
US8030354B2 (en) 2007-10-10 2011-10-04 Amgen Inc. Substituted biphenyl GPR40 modulators
US8450522B2 (en) 2008-03-06 2013-05-28 Amgen Inc. Conformationally constrained carboxylic acid derivatives useful for treating metabolic disorders
US8648208B2 (en) 2008-04-15 2014-02-11 Nippon Chemiphar Co. Ltd. Activating agent for peroxisome proliferator activated receptor
EP3424917A1 (fr) 2008-04-15 2019-01-09 Nippon Chemiphar Co., Ltd. Activateur du récepteur activé par proliférateur de peroxysome
WO2009128558A1 (fr) 2008-04-15 2009-10-22 日本ケミファ株式会社 Activateur pour récepteur activé par les proliférateurs de peroxysomes
US8822519B2 (en) 2008-08-07 2014-09-02 Zhejiang Hisun Pharmaceutical Co., Ltd. Compound with agitation effect on peroxisome proliferator-activated receptor process for its preparation and use thereof
WO2010015212A1 (fr) 2008-08-07 2010-02-11 浙江海正药业股份有限公司 COMPOSÉ AVEC EFFET D’AGITATION SUR LE RÉCEPTEUR δ ACTIVÉ PAR LES PROLIFÉRATEURS DE PEROXISOME ET UTILISATION DE CELUI-CI
US8748462B2 (en) 2008-10-15 2014-06-10 Amgen Inc. Spirocyclic GPR40 modulators
WO2010045361A1 (fr) 2008-10-17 2010-04-22 Metabolex, Inc. Procédés de réduction de petites particules denses de ldl
US11007162B2 (en) 2008-10-17 2021-05-18 Cymabay Therapeutics, Inc. Methods of reducing small, dense LDL particles
WO2012027331A1 (fr) 2010-08-27 2012-03-01 Ironwood Pharmaceuticals, Inc. Compositions et procédés pour traiter ou prévenir un syndrome métabolique et des maladies et troubles associés
US10456406B2 (en) 2013-09-09 2019-10-29 Vtv Therapeutics Llc Use of a PPAR-δ agonist for reducing loss of muscle strength, muscle mass, or type I muscle fibers in an immobilized limb
EP3756661A1 (fr) 2013-09-09 2020-12-30 vTv Therapeutics LLC Utilisation d'un agoniste de ppar-delta pour le traitement de l'atrophie musculaire
US11096946B2 (en) 2013-09-09 2021-08-24 Vtv Therapeutics Llc Use of a PPAR-δ agonist for reducing loss of muscle strength, muscle mass, or type I muscle fibers in an immobilized limb
EP3871667A4 (fr) * 2018-10-23 2022-08-17 Japan Science and Technology Agency Activateur de ppar?
US11634387B2 (en) 2019-09-26 2023-04-25 Abionyx Pharma Sa Compounds useful for treating liver diseases
WO2022189856A1 (fr) * 2021-03-08 2022-09-15 Abionyx Pharma Sa Composés utiles pour le traitement des maladies du foie
US11931365B2 (en) 2022-01-25 2024-03-19 Reneo Pharmaceuticals, Inc. Use of PPAR-delta agonists in the treatment of disease

Also Published As

Publication number Publication date
AR035320A1 (es) 2004-05-12
CZ20014664A3 (cs) 2002-03-13
JP2003313141A (ja) 2003-11-06
MY120090A (en) 2005-08-30
CA2377126A1 (fr) 2001-01-04
AU765347B2 (en) 2003-09-18
MXPA01013244A (es) 2002-07-02
ES2243276T3 (es) 2005-12-01
HUP0201858A3 (en) 2004-12-28
PE20010406A1 (es) 2001-04-10
CN1164579C (zh) 2004-09-01
PT1189895E (pt) 2005-10-31
NO20016078D0 (no) 2001-12-13
DE60020701D1 (de) 2005-07-14
IL146634A0 (en) 2002-07-25
NO20016078L (no) 2001-12-13
ATE297384T1 (de) 2005-06-15
KR20020015358A (ko) 2002-02-27
NO321872B1 (no) 2006-07-17
CA2377126C (fr) 2009-01-27
HK1042897A1 (en) 2002-08-30
GB9914977D0 (en) 1999-08-25
JP2003503399A (ja) 2003-01-28
US6710063B1 (en) 2004-03-23
EP1189895A1 (fr) 2002-03-27
EP1189895B8 (fr) 2005-11-09
AU5817100A (en) 2001-01-31
NZ515676A (en) 2004-05-28
DE60020701T2 (de) 2006-05-04
CN1358179A (zh) 2002-07-10
IL146634A (en) 2007-10-31
CZ300654B6 (cs) 2009-07-08
TR200103612T2 (tr) 2002-05-21
HK1042897B (zh) 2005-12-02
CO5180622A1 (es) 2002-07-30
US20030203947A1 (en) 2003-10-30
KR100668026B1 (ko) 2007-02-28
EP1189895B1 (fr) 2005-06-08
PL353135A1 (en) 2003-10-20
HUP0201858A2 (en) 2002-09-28
ZA200109804B (en) 2003-02-28
BR0011891A (pt) 2002-03-05
TWI256389B (en) 2006-06-11
US6723740B2 (en) 2004-04-20
JP3490704B2 (ja) 2004-01-26

Similar Documents

Publication Publication Date Title
EP1189895B1 (fr) Derives de thiazol et d'oxazole et utilisation pharmaceutique de ceux-ci
EP1343773B1 (fr) Derives thiazole destines au traitement de troubles associes a des recepteurs ppar
US6518290B1 (en) Substituted oxazoles and thiazoles derivatives as HPPAr alpha activators
AU2002312954B2 (en) Thiazole or oxazole derivatives which are useful in the treatment of cardiovascular and related diseases
AU2002246713A1 (en) Thiazole derivatives for treating PPAR related disorders
US20040147571A1 (en) Substituted oxazoles and thiazoles as hppar alpha agonists
WO2004000785A2 (fr) Composes chimiques
US7439259B2 (en) Thiazole derivatives for treating PPAR related disorders
US7157479B2 (en) Oxazol/thiazol-derivatives activators of the hPPAR-alpha receptor
US7141591B2 (en) 1,2,4-oxadiazole derivatives as hPPAR alpha agonists
AU2002220902A1 (en) 1, 2, 4-oxadiazole derivatives as hPPAR alpha agonists

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 00809496.9

Country of ref document: CN

AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WWE Wipo information: entry into national phase

Ref document number: 2000943847

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 515676

Country of ref document: NZ

Ref document number: IN/PCT/2001/1232/KOL

Country of ref document: IN

WWE Wipo information: entry into national phase

Ref document number: 58171/00

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: 2001/09804

Country of ref document: ZA

Ref document number: 200109804

Country of ref document: ZA

WWE Wipo information: entry into national phase

Ref document number: 2001/03612

Country of ref document: TR

WWE Wipo information: entry into national phase

Ref document number: PA/a/2001/013244

Country of ref document: MX

WWE Wipo information: entry into national phase

Ref document number: 2377126

Country of ref document: CA

Ref document number: 10018935

Country of ref document: US

WWE Wipo information: entry into national phase

Ref document number: PV2001-4664

Country of ref document: CZ

WWE Wipo information: entry into national phase

Ref document number: 1020017016616

Country of ref document: KR

ENP Entry into the national phase

Ref document number: 2001 507012

Country of ref document: JP

Kind code of ref document: A

WWP Wipo information: published in national office

Ref document number: 1020017016616

Country of ref document: KR

WWP Wipo information: published in national office

Ref document number: PV2001-4664

Country of ref document: CZ

WWP Wipo information: published in national office

Ref document number: 2000943847

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWG Wipo information: grant in national office

Ref document number: 58171/00

Country of ref document: AU

WWG Wipo information: grant in national office

Ref document number: 2000943847

Country of ref document: EP

WWG Wipo information: grant in national office

Ref document number: 1020017016616

Country of ref document: KR